The inflammatory reaction is the main cause of acute respiratory distress syndrome and multiple organ failure in patients with Coronavirus disease 2019, especially those with severe and critical ...illness. Several studies suggested that high-dose vitamin C reduced inflammatory reaction associated with sepsis and acute respiratory distress syndrome. This study aimed to determine the efficacy and safety of high-dose vitamin C in Coronavirus disease 2019.
We included 76 patients with Coronavirus disease 2019, classified into the high-dose vitamin C group (loading dose of 6g intravenous infusion per 12 hr on the first day, and 6g once for the following 4 days, n=46) and the standard therapy group (standard therapy alone, n=30).
The risk of 28-day mortality was reduced for the high-dose vitamin C versus the standard therapy group (HR=0.14, 95% CI, 0.03-0.72). Oxygen support status was improved more with high-dose vitamin C than standard therapy (63.9% vs 36.1%). No safety events were associated with high-dose vitamin C therapy.
High-dose vitamin C may reduce the mortality and improve oxygen support status in patients with Coronavirus disease 2019 without adverse events.
The regulation of detached ripening is significant for prolonging fruit shelf life. Although light quality and sucrose affecting strawberry fruit ripening have been widely reported, little ...information is available about how they co-regulate the strawberry detached ripening process. In this study, different light qualities (red light-RL, blue light-BL, and white light-WL) and 100 mM sucrose were applied to regulate the ripening of initial red fruits detached from the plant. The results showed RL-treated samples (RL + H
O, RL + 100 mM sucrose) had brighter and purer skin color with a higher L*, b*, and C* value, and promoted the ascorbic acid. Almost all light treatments significantly decreased TSS/TA (total soluble solid/titratable acid) and soluble sugar/TA ratio, which is exacerbated by the addition of sucrose. Blue or red light in combination with sucrose notably increased total phenolic content and decreased malondialdehyde (MDA) accumulation. In addition, blue or red light combined with sucrose increased abscisic acid (ABA) content and promoted ABA signaling by inducing ABA-INSENSITIVE 4 (
) expression and inhibiting SUCROSE NONFERMENTING1-RELATED PROTEIN KINASE 2.6 (
) expression. The strawberries exposed to blue and red light significantly improved auxin (IAA) content compared to the control (0 d), whereas the addition of sucrose inhibited IAA accumulation. Moreover, sucrose treatment suppressed the AUXIN/INDOLE-3-ACETIC ACID 11 (
) and AUXIN RESPONSE FACTOR 6 (
) expression under different light qualities. Overall, these results indicated that RL/BL + 100 mM sucrose might promote the detached ripening of strawberries by regulating abscisic acid and auxin signaling.
To date, immunotherapy has improved the 5-year survival rate of patients with advanced non-small cell lung cancer (NSCLC) from 4% to 15%. However, only 30%-50% of the NSCLC patients respond to immune ...checkpoint inhibitors (ICIs) immunotherapy. Therefore, screening patients for potential benefit with precise biomarkers may be of great value.
First, an immunotherapy NSCLC cohort was analyzed to identify the gene mutations associated with the prognosis of ICI treatment. Further analyses were conducted using NSCLC cohort in The Cancer Genome Atlas (TCGA) project to validate the correlations between the specific gene mutations and tumor immunogenicity, antitumor immunity, and alterations in the tumor-related pathways using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Gene set enrichment analysis (GSEA).
In the immunotherapy NSCLC cohort (n = 266), significantly longer overall survival (OS) rates were observed in the
-mutant type (PAK7-MT) group (n = 13) than the
-wild type (PAK7-WT) group (n = 253) (
= 0.049, HR = 0.43, 95%CI = 0.23-0.79). In the TCGA cohort,
mutations were correlated with the higher tumor mutation burden (TMB) (14.18
7.13,
0.001), increased neoantigen load (NAL) (7.52
4.30,
0.001), lower copy number variation (CNV), and higher mutation rate in the DNA damage response (DDR)-related pathways. In addition,
mutations were also positively correlated with immune-related genes expressions and infiltrating CD8+ T cells (0.079
0.054,
= 0.005). GSEA results showed that several tumor-related pathways varied in the PAK7-MT group, suggesting the potential mechanisms that regulate the tumor immune-microenvironment.
This study suggested that the
mutations might be a potential biomarker to predict the efficacy of immunotherapy for NSCLC patients. Considering the heterogeneity among the patients and other confounding factors, a prospective clinical trial is proposed to further validate the impact of
mutation on the immunotherapy outcomes in NSCLC.
Background and purpose
Besides cerebral collaterals, few studies have examined other additional factors affecting the prognosis of patients with large artery atherosclerotic (LAA) stroke. Our study ...aims to explore the effect of the cerebral small vessel disease (SVD) and the effects of its interaction with cerebral collaterals on the prognosis of patients with acute LAA stroke.
Method
Patients aged 18 years or older with LAA stroke within 24 h after stroke onset were consecutively enrolled. The functional outcome was determined using the modified Rankin Scale (mRS) at 3 months after stroke onset. Logistic multivariate analyses were used to identify the risk factors for stroke prognosis. Receiver operating characteristic (ROC) curves were constructed to compare the effects of cerebral collaterals and SVD on predicting the prognosis.
Results
Of the 274 enrolled patients, 174 (63.50%) were identified as having a favorable prognosis, and 100 (36.50%) were identified as having an unfavorable prognosis. After adjusting for covariates, the logistic regression analysis identified that unfavorable prognosis was related to the total SVD score (Model 1, adjusted odds ratio = 1.73, 95% CI: 1.15–2.61,
P
< 0.01; Model 2, adjusted odds ratio = 1.85, 95% CI: 1.23–2.79,
P
< 0.01) and Tan score (Model 1, adjusted odds ratio = 0.38, 95% CI: 0.23–0.64,
P
< 0.01; Model 2, adjusted odds ratio = 0.52, 95% CI: 0.33–0.82,
P
< 0.01). Compared with cerebral collaterals (AUC = 0.59; 95% CI: 0.52–0.67;
P
< 0.01) or SVD (AUC = 0.62; 95% CI: 0.56–0.69;
P
< 0.01) alone, the combination of collaterals and SVD (AUC = 0.66; 95% CI: 0.59–0.73;
P
< 0.01) had higher diagnostic value for an unfavorable prognosis, and the optimal sensitivity and specificity were 77.01 and 53.00%, respectively.
Conclusions
The total SVD burden was related to the prognosis of patients with LAA stroke. Compared with cerebral collaterals or SVD alone, cerebral collaterals combined with total SVD burden are better at predicting the prognosis of patients with acute LAA stroke.
•Mercury has been associated with female infertility, but the evidence supporting this is limited and controversial.•There was no linear association between the total blood mercury and infertility in ...a univariate or multivariate analysis.•Total blood mercury was non-linear associated with infertility when it >5.278 μg/L (OR 2.57; 95% CI 1.12, 5.87).
Mercury is a ubiquitous toxic heavy metal associated with an increased risk of female infertility; however, the evidence supporting this is limited and controversial. We aimed to explore the relationship between the total blood mercury and infertility in 1796 selected participants from the National Health and Nutrition Examination Survey (NHANES) (2013–2016). We found no significant association between mercury and infertility based on a fully-adjusted model (OR 1.04; 95 % CI 0.91, 1.19), and the results remained robust in a series of sensitive analysis. However, a non-linear relationship was detected. By a two-piecewise linear regression model and recursive algorithm, we identified an inflection point of 5.278 μg/L, when blood mercury was >5.278 μg/L, a 1-unit increase in mercury (log2) was associated with 157 % greater adjusted odds of infertility (OR 2.57; 95 % CI 1.12, 5.87). Our findings provide new insights to advance the research of the link between mercury and infertility.
A novel Al-Mg-Si aluminum alloy with the addition of the micro-alloying element Er and Zr that was promptly quenched after extrusion has been studied. The solid solution and aging treatment of the ...novel alloy are studied by observing the microstructure, mechanical properties, and strengthening mechanism. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques are employed to examine the changes in the microstructure resulting from various solid solution treatments and aging treatments. The best strengthening effect can be achieved when the solubility of the MgSi phase and precipitate β″ (Mg2Si phase) is at their maximum. The addition of Er and Zr elements promotes the precipitation of the β″ phase and makes the b″ phase more finely dispersed. The aging strengthening of alloys is a comprehensive effect of the dislocation cutting mechanism and bypass mechanism, the joint effect of diffusion strengthening of Al3(Er,Zr) particles and the addition of Er and Zr elements promoting the precipitation strengthening of β″ phases. In this paper, by adding Er and Zr elements and exploring the optimal heat treatment system, the yield strength of the alloy reaches 437 MPa and the tensile strength reaches 453 MPa after solid solution treatment at 565 °C/30 min and aging at 175 °C/10 h.
RNA interference (RNAi) has been thought to be a gene-silencing pathway present in most eukaryotic cells to safeguard the genome against retrotransposition. Small interfering RNAs (siRNAs) have also ...become a powerful tool for studying gene functions. Given the endosymbiotic hypothesis that mitochondria originated from prokaryotes, mitochondria have been generally assumed to lack active RNAi; however, certain bacteria have Argonaute homologs and various reports suggest the presence of specific microRNAs and nuclear genome (nDNA)-encoded Ago2 in the mitochondria. Here we report that transfected siRNAs are not only able to enter the matrix of mitochondria, but also function there to specifically silence targeted mitochondrial transcripts. The mitoRNAi effect is readily detectable at the mRNA level, but only recordable on relatively unstable proteins, such as the mtDNA-encoded complex IV subunits. We also apply mitoRNAi to directly determine the postulated crosstalk between individual respiratory chain complexes, and our result suggests that the controversial observations previously made in patient-derived cells might result from differential adaptation in different cell lines. Our findings bring a new tool to study mitochondrial biology.
Objective
Dexamethasone (DEX), a synthetic glucocorticoid, has been widely used as a medication for premature delivery. However, the side effects of antenatal DEX treatment on fetal bone development, ...as well as the underlying mechanisms still remain to be elucidated. Here, we aimed to explore the effects and the related mechanisms of antenatal DEX exposure during late pregnancy on fetal bone growth and development.
Methods
Pregnant Sprague–Dawley rats were randomly divided into DEX group and vehicle group from gestational day 14 (GD14). Pregnant rats in DEX group were intraperitoneally injected once with DEX (200 µg/kg body weight) on GD14, 16, 18, and 20. The vehicle group rats were administered the same amount of normal saline at the same time. Pregnant rats were anesthetized at GD21 to harvest fetal femurs for analysis.
Results
Antenatal DEX treatment delayed fetal skeletal growth via inhibiting extracellular matrix (ECM) synthesis and downregulating insulin-like growth factor 1 (IGF1) signaling. Several components of IGF1 signaling pathway, including IGF1 receptor, insulin receptor substrate, as well as serine–threonine protein kinase, were down-regulated in fetal growth plate chondrocytes following DEX treatment.
Conclusion
This study indicated that antenatal DEX treatment-retarded fetal skeletal growth was associated with the down-regulation of IGF1 signaling in growth plate chondrocytes, providing important information about the impact of antenatal DEX application four courses on premature infant.
Glycerol-induced resistance to various pathogens has been reported in different plants. Glycerol kinase (GK), a vital rate-limiting enzyme that catalyzes glycerol conversion to glycerol-3-phosphate ...(G3P), participates in responses to both abiotic and biotic stresses. However, its physiological importance in rice defenses against pathogens remains unclear. In this research, quantification analysis revealed that GK levels were significantly induced in rice leaves infected by
pv.
strain PXO99. A typical GK-encoding gene
was cloned in rice. The transcriptional levels of
were significantly induced by salicylic acid, jasmonic acid, and
PXO99. Ectopic expression of
partially rescued the resistance to
in the
mutant. In the overexpressing transgenic rice lines (
-OE), the content of GK and the transcriptional level of
were increased and the resistance to bacterial blight and blast was improved, while reduced
expression impaired the resistance in
-RNAi lines. The wax contents and expression of the wax synthesis regulatory genes were significantly increased in the overexpression lines but decreased in the
-RNAi lines. We then confirmed the interaction partner of OsNHO1 using yeast two-hybrid and bimolecular fluorescence complementation assays. The transcription of the interaction partner-encoding genes
and
in
-RNAi lines was downregulated but upregulated in
-OE lines. Thus, we concluded that
provided disease resistance by affecting the wax content and modulating the transcription levels of
genes.
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